The leader of the Natural Products Association (NPA) slammed his former employer—the FDA—for not rigorously enforcing a notification requirement in U.S. law while commenting on a draft guidance published last week.
The FDA guidance, once finalized, would give distributors and manufacturers of new dietary ingredients (NDIs) 180 days to submit identity and safety data to the agency without fear of reprisal for failing to timely meet a premarket notification requirement in the Dietary Supplement Health and Education Act of 1994 (DSHEA).
To encourage firms to remedy past failures to meet the statutory obligation, FDA said it intends to “exercise enforcement discretion” regarding “the premarket notification requirement … for a limited time and under limited circumstances.”
“We remain committed to a flexible framework for dietary supplements that ensures the safety of these products for consumers,” said Cara Welch, Ph.D., director of FDA’s Office of Dietary Supplement Programs (ODSP), in a May 19 press release. “The resulting notifications the agency receives through this period of enforcement discretion will help increase the amount of safety information we have about NDI-containing dietary supplements in the marketplace.”
Dan Fabricant, president and CEO of NPA, doesn’t believe there will be meaningful improvement in compliance with the NDI notification (NDIN) requirement until FDA enforces against non-compliant firms.
“They really gave [NDI enforcement] no consideration even when things were presented to them like beta-alanine,” Fabricant said, commenting on an ingredient that was the subject of a four-part series of articles published by Natural Products Insider. “They were just like, ‘Yah, not interested.’”
Fabricant and others have urged FDA to enforce against “copycat” NDIs, whose identity and safety information has not been reviewed by FDA, but which may resemble an ingredient that has been the subject of a successful notification to the agency.
“Until there’s enforcement on the copycats ... this is all pointless,” said Fabricant, who led FDA’s Division of Dietary Supplement Programs from 2011 until 2014.
“Here’s what’s more troubling … FDA is going to decide to enforce when they want to enforce,” Fabricant said in an interview. “This is a problem we’ve been pointing out to them” since at least 2019.
“It should have been a priority for the past four years,” he added. “That tells you there’s so much disrepair at the organization.”
Asked whether FDA’s objective in the draft guidance—to increase the identity and safety information it has on NDIs—is laudable, Fabricant responded, “Hasn’t that always been the goal?”
“This shouldn’t be like an initiative that’s being announced,” he said, commenting on the NDIN requirement. “This is in the statute. This is in there in black and white.”
Mark LeDoux is chairman and CEO of Natural Alternatives International Inc. (NAI), a manufacturer of nutritional supplements, which provided FDA data in 2018 to demonstrate the identity and safety of its NDI, CarnoSyn beta-alanine. NAI spent at least $1 million investing in the NDIN process, and the figure is more than twice that amount when including human clinical trials to support components of the submission, he previously told Natural Products Insider.
“For some unknown reason, based on a theory of enforcement discretion, the agency is now asking industry to comply with the legal requirement to file NDIs for substances already in the marketplace,” LeDoux remarked in an email last week.
LeDoux, who also chairs NPA’s board of directors, asked, “Is the standard for following the law somehow related to the apparent safety of general use of adulterated products, or should companies actually follow the letter of the law requiring NDI submissions for substances that were not part of general commerce and ingestion prior to the passage of DSHEA in 1994?”
FDA suspects many firms—and thousands of NDIs—subject to the notification requirement have failed to provide FDA the required safety information. An FDA official in 2019 estimated there were 4,600 new dietary ingredient notifications required, but only about 1,200 notifications have been submitted to FDA to date since DSHEA's passage.
Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), applauded FDA’s plans to give firms an “amnesty period” to submit their NDINs, and he encouraged firms subject to the requirement to provide their information to FDA establishing the safety of their products.
“Unfortunately, the concerns the agency expressed are partially of its own making by failing to provide a clear direction for when an NDI notification is required and failing to enforce the existing requirements,” Mister said in a written statement.
For example, he said FDA has not accepted as “authoritative” or developed an authoritative list of dietary ingredients marketed in the U.S. before Oct. 15, 1994. These “old” or “grandfathered” dietary ingredients are exempt from the NDIN requirement.
FDA still has not finalized a guidance clarifying when an ingredient is new and subject to the notification requirement. The agency first published a draft guidance in July 2011, then supplanted it with a 102-page draft guidance in August 2016. In that document, FDA said it was “prepared to develop an authoritative list of pre-DSHEA ingredients, based on independent and verifiable data.” As Mister observed, such a list has not been developed.
The 2016 draft guidance caused several areas of disagreement between industry and FDA, such as when a manufacturing change constitutes a “chemical alteration” and triggers the notification requirement for a conventional food ingredient.
Instead of addressing the issues that require “more technical clarity, [FDA officials] just said, ‘Nah, we’re not going to deal with that. We’re going to deal with what we want to deal with,’” Fabricant said.
Mister joined Fabricant in criticizing FDA for failing to sufficiently enforce the NDIN requirement.
“Three years ago, CRN proposed a master file system to the agency to protect ingredient innovation and incentivize firms to submit NDI notifications with the assurance that their intellectual property would be protected—but FDA declined to provide the enforcement required to make the system work,” Mister said in his statement.
“Much uncertainty still exists as to when an ingredient is ‘new’ and subject to the notification requirement," Mister added. “FDA cannot expect firms to submit their safety dossiers and manufacturing processes for possible objection when it provides neither meaningful consequences for the failure to file nor a clear roadmap for when an NDI notification is necessary. Enforcement discretion would be better enacted after the above issues are resolved.”
Duffy MacKay, senior vice president of dietary supplements with the Consumer Healthcare Products Association (CHPA), also stressed the importance of enforcing the NDIN requirement.
“It’s in the mutual interest of consumers and industry for FDA to protect against ingredients that don’t meet safety standards,” MacKay said in a statement. “That’s why responsible members of the dietary supplement industry who are advocating for regulatory modernization also recognize that current safety regulations need to be enforced, including NDIN requirements. At first glance, CHPA appreciates FDA’s renewed interest in enforcing the NDIN provision of DSHEA.”
He added CHPA will be reviewing the draft guidance with its members and plans to submit formal comments with FDA by the deadline. FDA requested stakeholders comment on the document within 60 days of publication in the Federal Register (May 20) before it begins work on a final version.